Energy drinks mixed with alcohol: what are the risks?
Energy drinks are popular beverages that typically include high levels of caffeine and other ingredients such as taurine, or caffeine-containing herbs, such as guarana. While energy drinks are often consumed alone, they are also frequently used as mixers for alcoholic beverages. This review summarizes what is known about the scope of use of alcohol mixed with energy drinks, the risks associated with such mixtures, and the objective laboratory data examining how the effects of their consumption differ from consuming alcohol alone. The weight of the evidence reveals that consuming alcohol mixed with energy drinks is riskier than consuming alcohol alone and constitutes a public health concern. Consumption of these mixed beverages is frequent, especially in young and underage drinkers, and compared with alcohol alone, their use is associated with elevated rates of binge drinking, impaired driving, risky sexual behavior, and risk of alcohol dependence. Laboratory research (human and animal) has demonstrated that consuming alcohol mixed with energy drinks leads to altered subjective states including decreased perceived intoxication, enhanced stimulation, and increased desire to drink/increased drinking compared to consuming alcohol alone. Possible underlying mechanisms explaining these observations are highlighted in this review.


Cerebral and non-cerebral coenurosis in small ruminants.
Cerebral coenurosis is caused by Coenurus cerebralis, the larval stage of Taenia multiceps. The metacestode causes severe lesions in the brain and spinal cord of the intermediate host, so-called "gid" or "stagger" disease. Whereas, the non-cerebral coenurosis caused by Coenurus gaigeri, the larval stage of Taenia gaigeri, particularly affects goats. The cyst form of the Taenia gaigeri is found in intramuscular and subcutaneous tissues. The difference in the sequence of mitochondrial genes of cox1 and nadI and also other variations reported for clinical, morphological and pathological aspects in coenurosis lead to the hypothesis that there is genetic intraspecific variability within this species, such as in other members of the genus Taenia. Nevertheless, it has been shown that sheep and goats have been infected by both cerebral and non-cerebral coenurosis and it has been suggested that such cerebral and non-cerebral metacestodes may belong to different species of Taenia which are host specific for these hosts.


Treatment of giant intracranial aneurysms using the Pipeline flow-diverting stent: Long-term results from the International Retrospective Study of the Pipeline Embolization Device (IntrePED) study.
Traditional endovascular treatments of giant intracranial aneurysms are associated with high rates of complications and retreatment. Our objective was to examine the safety and long-term efficacy of the Pipeline Embolization Device for treatment of these aneurysms. This retrospective study using the IntrePED database included all patients with giant intracranial aneurysms treated with the Pipeline device between July 2008 and February 2013. Efficacy outcomes were stratified by using the Raymond-Roy Occlusion Classification. Predefined safety outcomes included spontaneous rupture of the target aneurysm; ipsilateral intracranial hemorrhage; ischemic stroke; parent artery stenosis; and sustained cranial neuropathy. Sixty-six embolizations were performed to treat 63 giant intracranial aneurysms (including 2 ruptured): 49 (77.8%) in the anterior and 14 (22.2%) in the posterior circulation. The median follow-up was 22.4 (0.1-60.5) months. Class I angiographic occlusion was achieved in 72.0% (36/50). The neurological morbidity/mortality rate was 23.8% (15/63), with higher rates in the posterior circulation than in the anterior circulation (22.4% vs. 28.6%). Among seven deaths, five had neurological causes. The procedure-related neurological morbidity and mortality rates were 22.7% (15/66) and 7.6% (5/66), respectively. The spontaneous rupture rate was 4.5% (3/66). Two spontaneous ruptures (1 death), 4/4 postprocedural intracranial hemorrhages, and 6/9 ischemic events occurred within 30 days. In-stent stenosis and new-onset cranial neuropathy were not observed during the angiographic follow-up period. Although procedure-related neurological morbidity/mortality rates were not insignificant, this study confirms the feasibility and long-term efficacy of the Pipeline Embolization Device to treat giant intracranial aneurysms.


Clarifying the Definition of Nonsuicidal Self-Injury.
Background: Challenges and inconsistencies in defining nonsuicidal self-injury (NSSI) have persisted for decades, which significantly impact NSSI conceptualization and assessment in clinical and research settings and impede the field's progress. Aims: The present study aimed to solicit opinions from individuals with NSSI expertise so as to improve the operational definition and conceptualization of NSSI. Method: We asked researchers, clinicians, and graduate students with varying NSSI expertise to provide opinions on six NSSI definitional components (e.g., whether pain should be a required outcome), as well as to review 118 behaviors and indicate whether each is NSSI. Results: Responses (N = 159) revealed good agreement on specific NSSI definitional aspects and the classification of oft-cited NSSI behaviors. However, findings also demonstrated potential discrepancies in how clinicians and researchers define NSSI when compared with specific behaviors that might be classified as NSSI. Limitations: The opinions of the study's sample may not reflect the wider NSSI field. Conclusion: Findings suggest that there is an increased need for a clear and consistent definition of NSSI and specific NSSI behaviors. There is also a need to develop new assessment measures that capture the range of NSSI behaviors that received good-to-excellent agreement among self-injury experts.


The EuroPhysiome, STEP and a roadmap for the virtual physiological human.
Biomedical science and its allied disciplines are entering a new era in which computational methods and technologies are poised to play a prevalent role in supporting collaborative investigation of the human body. Within Europe, this has its focus in the virtual physiological human (VPH), which is an evolving entity that has emerged from the EuroPhysiome initiative and the strategy for the EuroPhysiome (STEP) consortium. The VPH is intended to be a solution to common infrastructure needs for physiome projects across the globe, providing a unifying architecture that facilitates integration and prediction, ultimately creating a framework capable of describing Homo sapiens in silico. The routine reliance of the biomedical industry, biomedical research and clinical practice on information technology (IT) highlights the importance of a tailor-made and robust IT infrastructure, but numerous challenges need to be addressed if the VPH is to become a mature technological reality. Appropriate investment will reap considerable rewards, since it is anticipated that the VPH will influence all sectors of society, with implications predominantly for improved healthcare, improved competitiveness in industry and greater understanding of (patho)physiological processes. This paper considers issues pertinent to the development of the VPH, highlighted by the work of the STEP consortium.


Construct validity of the Psychopathic Personality Inventory in a correctional sample.
The relations between the Psychopathic Personality Inventory (PPI; Lilienfeld & Andrews, 1996) and 4 theoretically related constructs (empathy, aggression, work ethic, and borderline personality disorder) were examined. Additionally, the relation between the PPI and heroism was explored. One hundred male inmates were administered the PPI, the Questionnaire Measure of Emotional Empathy (Mehrabian & Epstein, 1972), the Aggression Questionnaire (Buss & Perry, 1992), the Protestant Ethic Scale (Mirels & Garrett, 1971), the Self-Report for Borderline Personality Scale (Oldham et al., 1985), and the Activity Frequency Inventory (Lilienfeld, 1998). As predicted, the PPI was significantly negatively correlated with empathy and significantly positively related to aggression and borderline personality. Contrary to prediction, the correlation between the PPI and work ethic was not significant. Eight of 11 hypotheses regarding the relations of the PPI subscales to these 4 constructs were corroborated. Results support the construct validity of the PPI in a correctional sample. The exploratory analysis of the relation between the PPI and heroism revealed no significant relations.


Intraosseous calcifications in tophaceous gout.
Intraosseous calcification in association with gouty arthritis was observed in six patients and a single cadaver. This finding, which is usually associated with chronic tophaceous gout, extensive articular destruction, and severe renal disease, is usually seen in the hands, wrists, and feet. It may be associated with additional calcific deposits in the adjacent soft tissues. Although the radiographic appearance of the calcification simulates that of an enchondroma or bone infarct, the abnormality seems related to intraosseous penetration of calcified urate deposits.


The chemistry of the reaction determines the invariant amino acids during the evolution and divergence of orotidine 5'-monophosphate decarboxylase.
Orotidine 5'-phosphate (OMP) decarboxylase has the largest rate enhancement for any known enzyme. For an average protein of 270 amino acids from more than 80 species, only 8 amino acids are invariant, and 7 of these correspond to ligand-binding residues in the crystal structures of the enzyme from four species. It appears that the chemistry required for catalysis determines the invariant residues for this enzyme structure. A motif of three invariant amino acids at the catalytic site (DXKXXD) is also found in the enzyme hexulose-phosphate synthase. Although the core of OMP decarboxylase is conserved, it has undergone a variety of changes in subunit size or fusion to other protein domains, such as orotate phosphoribosyltransferase, during evolution in different kingdoms. The phylogeny of OMP decarboxylase shows a unique subgroup distinct from the three kingdoms of life. The enzyme subunit size almost doubles from Archaea (average mass of 24.5 kDa) to certain fungi (average mass of 41.7 kDa). These observed changes in subunit size are produced by insertions at 12 sites, largely in loops and on the exterior of the core protein. The consensus for all sequences has a minimal size of <20 kDa.


Expression and function of class II antigens on gastric carcinoma cells and gastric epithelia: differential expression of DR, DQ, and DP antigens.
The expression of human histocompatibility leukocyte antigen class II antigens on gastric epithelia and gastric carcinoma (GaCa) was studied with the use of murine monoclonal antibodies to DR, DQ, and DP antigens. DR and DP antigens but not DQ antigens were demonstrated in fundic glands of normal gastric epithelia, and DP+ cells were located in part of the DR+ epithelia. Of 15 GaCas examined, 11 expressed DR antigen, and the degree of the expression varied considerably among the specimens. DP antigen was found in 3 of the 11 DR+ carcinomas, and the DQ antigen was found in one of the 3 DR+ DP+ specimens. Thus the expression of class II antigens in normal gastric epithelia and GaCas appears to be in the order of DR, DP, and DQ. Studies on 3 GaCa cell lines (Kato III, MKN28, and MKN45) demonstrated that 1 line (Kato III) expressed DR antigen only, and the remaining lines were negative. Interferon (IFN)-gamma treatment enhanced the expression of DR antigen on Kato III cells and induced expression of DQ and DP antigens. The IFN-gamma treatment also induced expression of DR antigen but not DQ or DP antigens in 1 of the 2 negative cell lines. The induction of the class II antigens by IFN-gamma was shown to be dose dependent. However, maximal induction of DQ and DP antigens on the Kato III cells and DR antigens on MKN45 cells required 10 times more IFN-gamma than that needed for the maximal expression of DR antigen on Kato III. Northern blot analyses of cytoplasmic RNA from these cells were in agreement with and affirmed the above-described expression of the class II antigens on the cell lines. The DR antigen on the Kato III cells was capable of stimulating allogeneic lymphocytes in MLR, and its stimulatory activity was significantly enhanced by IFN-gamma. These results demonstrated a differential expression of class II antigens in the "DR, DP, and DQ order" in normal gastric epithelia, GaCa cells, and GaCa cell lines, suggesting different mechanisms acting discordantly on the expression of each of these antigens and that the DR antigen on the GaCa cell lines possesses MLR-stimulatory ability.


ELF exposure from mobile and cordless phones for the epidemiological MOBI-Kids study.
This paper describes measurements and computational modelling carried out in the MOBI-Kids case-control study to assess the extremely low frequency (ELF) exposure of the brain from use of mobile and cordless phones. Four different communication systems were investigated: Global System for Mobile (GSM), Universal Mobile Telecommunications System (UMTS), Digital Enhanced Cordless Telecommunications (DECT) and Wi-Fi Voice over Internet Protocol (VoIP). The magnetic fields produced by the phones during transmission were measured under controlled laboratory conditions, and an equivalent loop was fitted to the data to produce three-dimensional extrapolations of the field. Computational modelling was then used to calculate the induced current density and electric field strength in the brain resulting from exposure to these magnetic fields. Human voxel phantoms of four different ages were used: 8, 11, 14 and adult. The results indicate that the current densities induced in the brain during DECT calls are likely to be an order of magnitude lower than those generated during GSM calls but over twice that during UMTS calls. The average current density during Wi-Fi VoIP calls was found to be lower than for UMTS by 30%, but the variability across the samples investigated was high. Spectral contributions were important to consider in relation to current density, particularly for DECT phones. This study suggests that the spatial distribution of the ELF induced current densities in brain tissues is determined by the physical characteristics of the phone (in particular battery position) while the amplitude is mainly dependent on communication system, thus providing a feasible basis for assessing ELF exposure in the epidemiological study. The number of phantoms was not large enough to provide definitive evidence of an increase of induced current density with age, but the data that are available suggest that, if present, the effect is likely to be very small.


Prenatal isolated mild ventriculomegaly is associated with persistent ventricle enlargement at ages 1 and 2.
Enlargement of the lateral ventricles is thought to originate from abnormal prenatal brain development and is associated with neurodevelopmental disorders. Fetal isolated mild ventriculomegaly (MVM) is associated with the enlargement of lateral ventricle volumes in the neonatal period and developmental delays in early childhood. However, little is known about postnatal brain development in these children. Twenty-eight children with fetal isolated MVM and 56 matched controls were followed at ages 1 and 2 years with structural imaging on a 3T Siemens scanner and assessment of cognitive development with the Mullen Scales of Early Learning. Lateral ventricle, total gray and white matter volumes, and Mullen cognitive composite scores and subscale scores were compared between groups. Compared to controls, children with prenatal isolated MVM had significantly larger lateral ventricle volumes at ages 1 and 2 years. Lateral ventricle volume at 1 and 2 years of age was significantly correlated with prenatal ventricle size. Enlargement of the lateral ventricles was associated with increased intracranial volumes and increased gray and white matter volumes. Children with MVM had Mullen composite scores similar to controls, although there was evidence of delay in fine motor and expressive language skills. Children with prenatal MVM have persistent enlargement of the lateral ventricles through the age of 2 years; this enlargement is associated with increased gray and white matter volumes and some evidence of delay in fine motor and expressive language development. Further study is needed to determine if enlarged lateral ventricles are associated with increased risk for neurodevelopmental disorders.


[On the issue of the development of municipal public health system].
The municipal public health is the basic sector of the actual health care system functioning in the Russian Federation nowadays. The research data from the Sverdlovskaya oblast revealed that today for the region development process was characterized by marked disproportions in the state of population health of municipal formations, in the local health care resources and in the effectiveness of their use. The implementation of multi-factorial analysis permitted to reveal the significant impact of public health on the development of the medical demographic situation in the municipal formations. Various choices of optimizing the public health management in the regions are discussed.


Antibody response to aggregated human interferon alpha2b in wild-type and transgenic immune tolerant mice depends on type and level of aggregation.
The aim of this study was to determine the sensitivity of transgenic immune tolerant mice for the type and level of aggregation of recombinant human interferon alpha2b (rhIFNalpha2b). RhIFNalpha2b was aggregated by metal-catalyzed oxidation or by incubation at elevated temperature and various pHs. Native rhIFNalpha2b was mixed with oxidized rhIFNalpha2b at different ratios to obtain samples with different aggregation levels. The preparations were characterized by UV and fluorescence spectroscopy, gel permeation chromatography (GPC), dynamic light scattering (DLS), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, and ELISA. The immunogenicity was evaluated in wild-type mice and transgenic mice immune tolerant for hIFNalpha2. Sera were analyzed by ELISA for the presence of rhIFNalpha2b-specific antibodies. The oxidized and aged preparations widely differed regarding the level and nature of aggregates. All preparations containing aggregates increased the immune response in the wild-type mice as compared to native rhIFNalpha2b and were able to break the tolerance of the transgenic mice. The more native-like the conformation of the aggregated proteins, the more immunogenic the preparations were in the transgenic mice. The native-like aggregates prepared via metal catalysis induced a dose-dependent loss of tolerance in the transgenic mice. In conclusion, the transgenic mouse model can be used to screen rhIFNalpha2b formulations for low levels of immunogenic aggregates obtained under accelerated storage conditions.


Enhanced production of cellobiohydrolases in Trichoderma reesei and evaluation of the new preparations in biofinishing of cotton.
In the search for suitable cellulase combinations for industrial biofinishing of cotton, five different types of Trichoderma reesei strains were constructed for elevated cellobiohydrolase production: CBHI overproducers with and without endoglucanase I (EGI), CBHII overproducers with and without endoglucanase II (EGII) and strains overproducing both CBHI and CBHII without the major endoglucanases I and II. One additional copy of cbh1 gene increased production of CBHI protein 1.3-fold, and two copies 1.5-fold according to ELISA (enzyme-linked immunosorbent assay). The level of total secreted proteins was increased in CBHI transformants as compared to the host strain. One copy of the cbh2 expression cassette in which the cbh2 was expressed from the cbh1 promoter increased production of CBHII protein three- to four-fold when compared to the host strain. T. reesei strains producing elevated amounts of both CBHI and CBHII without EGI and EGII were constructed by replacing the egl1 locus with the coding region of the cbh1 gene and the egl2 locus with the coding region of cbh2. The cbh1 was expressed from its own promoter and the cbh2 gene using either the cbh1 or cbh2 promoter. Production of CBHI by the CBH-transformants was increased up to 1.6-fold and production of CBHII up to 3.4-fold as compared with the host strain. Approximately similar amounts of CBHII protein were produced by using cbh1 or cbh2 promoters. When the enzyme preparation with elevated CBHII content was used in biofinishing of cotton, better depilling and visual appearance were achieved than with the wild type preparation; however, the improvement was not as pronounced as with preparations with elevated levels of endoglucanases (EG).


Glucagon-Like Peptide-1 Increases Mitochondrial Biogenesis and Function in INS-1 Rat Insulinoma Cells.
Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases glucose-stimulated insulin secretion in pancreatic β-cells. Since mitochondrial function is crucial to insulin secretion, we hypothesized that GLP-1 may increase mitochondrial biogenesis in pancreatic β-cells. We treated INS-1 rat insulinoma cells with GLP-1 or exendin-4 for 48 hours and measured mitochondrial mass and function. Both GLP-1 and exendin-4 increased mitochondrial mass by approximately 20%. The mitochondria/cytosol ratio was increased from 7.60±3.12% to 10.53±2.70% by exendin-4. In addition, GLP-1 increased the mitochondrial membrane potential and oxygen consumption. Proliferator-activated receptor-gamma coactivator 1α expression was increased approximately 2-fold by GLP-1 treatment. In conclusion, the present study presents evidence for a new mechanism of action by which GLP-1 improves pancreatic β-cell function via enhanced mitochondrial mass and performance.


Self-regulated learning in the clinical context: a systematic review.
Research has suggested beneficial effects of self-regulated learning (SRL) for medical students' and residents' workplace-based learning. Ideally, learners go through a cyclic process of setting learning goals, choosing learning strategies and assessing progress towards goals. A clear overview of medical students' and residents' successful key strategies, influential factors and effective interventions to stimulate SRL in the workplace is missing. This systematic review aims to provide an overview of and a theoretical base for effective SRL strategies of medical students and residents for their learning in the clinical context. This systematic review was conducted according to the guidelines of the Association for Medical Education in Europe. We systematically searched PubMed, EMBASE, Web of Science, PsycINFO, ERIC and the Cochrane Library from January 1992 to July 2016. Qualitative and quantitative studies were included. Two reviewers independently performed the review process and assessed the methodological quality of included studies. A total of 3341 publications were initially identified and 18 were included in the review. We found diversity in the use of SRL strategies by medical students and residents, which is linked to individual (goal setting), contextual (time pressure, patient care and supervision) and social (supervisors and peers) factors. Three types of intervention were identified (coaching, learning plans and supportive tools). However, all interventions focused on goal setting and monitoring and none on supporting self-evaluation. Self-regulated learning in the clinical environment is a complex process that results from an interaction between person and context. Future research should focus on unravelling the process of SRL in the clinical context and specifically on how medical students and residents assess their progress towards goals.


Use of polymerase chain reaction-amplified Helicobacter pylori urease structural genes for differentiation of isolates.
Helicobacter pylori has been demonstrated as an etiologic agent of human gastritis and peptic ulcer formation. However, there is no straightforward basis to distinguish different isolates. We used the polymerase chain reaction (PCR) to amplify the urease structural subunit genes, ureA and ureB, which, when digested with appropriate restriction endonucleases, allow the differentiation of patterns on agarose gels. PCR amplification was possible with DNA rapidly extracted from H. pylori by alkaline lysis and phenol-chloroform. The 2.4-kb PCR products amplified from 22 clinical isolates and subjected to HaeII restriction endonuclease digestion produced 10 distinct patterns on agarose gels, with two patterns being shared between five and six strains. PCR amplification of the urease genes may enable the differentiation of closely related H. pylori strains by restriction digest analysis of PCR-amplified ureA and ureB genes.


THe effects of the gut microflora and dietary fibre on energy utilization by the chick.
1. Groups of adult colostimized chickens were given diets with and without dietary fibre in the form of bagasse or wheat straw. The fibrous materials were analysed for their contents of cellulose, hemicellulose and lignin. The digestible energies (DE) and metabolizable energies (ME) of these diets were measured by a balance method. 2. Groups of germ-free and conventional chicks aged 4 weeks were given diets with and without penicillin or with and without graded levels of wheat straw as a source of fibre and the ME of these diets were determined. 3. The incorporation of the forms of dietary fibre tested reduced the DE and the ME of the diets in adult conventional chickens and the ME in young germ-free and conventional chicks. Both DE and ME were reduced in proportions that suggested that the dietary fibre present was acting largely as an inactive diluent of the dietary energy and was not affecting the absorption of other nutrients. In the young germ-free and conventional chicks, there was a linear relationship between the proportion of wheat straw in one diet and the reduction ME. 4. Dietary penicillin did not alter the ME of the diet in either the germ-free or the conventional environments. 5. The reduction of ME with incorporation of wheat straw was less in conventional than in germ-free chicks. It is suggested that this may be due to the ability of chicks with a gut flora to obtain a small amount of energy from wheat straw.


Chemical and microbial remediation of hexavalent chromium from contaminated soil and mining/metallurgical solid waste: a review.
Chromium is a highly toxic non-essential metal for microorganisms and plants, and its occurrence is rare in nature. Lower to higher chromium containing effluents and solid wastes released by activities such as mining, metal plating, wood preservation, ink manufacture, dyes, pigments, glass and ceramics, tanning and textile industries, and corrosion inhibitors in cooling water, induce pollution and may cause major health hazards. Besides, natural processes (weathering and biochemical) also contribute to the mobility of chromium which enters in to the soil affecting the plant growth and metabolic functions of the living species. Generally, chemical processes are used for Cr- remediation. However, with the inference derived from the diverse Cr-resistance mechanism displayed by microorganisms and the plants including biosorption, diminished accumulation, precipitation, reduction of Cr(VI) to Cr(III), and chromate efflux, bioremediation is emerging as a potential tool to address the problem of Cr(VI) pollution. This review focuses on the chemistry of chromium, its use, and toxicity and mobility in soil, while assessing its concentration in effluents/wastes which becomes the source of pollution. In order to conserve the environment and resources, the chemical/biological remediation processes for Cr(VI) and their efficiency have been summarised in some detail. The interaction of chromium with various microbial/bacterial strains isolated and their reduction capacity towards Cr(VI) are also discussed.


Neuromuscular and Cardiovascular Adaptations in Response to High-Intensity Interval Power Training.
Romero-Arenas, S, Ruiz, R, Vera-Ibáñez, A, Colomer-Poveda, D, Guadalupe-Grau, A, and Márquez, G. Neuromuscular and cardiovascular adaptations in response to high-intensity interval power training. J Strength Cond Res 32(1): 130-138, 2018-The aim of this study was to determine the efficacy of a high-intensity power training (HIPT) program, and to compare the effects of HIPT to traditional power training (TPT) on the aerobic and power performance. For this purpose, 29 healthy men (23.1 ± 2.7 years) were recruited and randomly distributed into 3 different groups. One group performed TPT (n = 10), the second group performed power training organized as a circuit (HIPT; n = 10), and the third group served as control group (CG; n = 9). Training consisted of weightlifting thrice per week for 6 weeks. The TPT subjects performed 3 to 5 sets of each exercises with interset rest of 90 seconds, and HIPT subjects executed the training in a short circuit (15 seconds of rest between exercises). To know the effects in aerobic performance, maximal aerobic speed (MAS) was measured. To identify the effects on power performance, subjects performed a Wingate test, a countermovement jump (CMJ) test, and a power-load curve in bench press. The main results showed that after both power training protocols, subjects increased significantly (p ≤ 0.05) the power production during the Wingate Test, the height and power reached during the CMJ test, and the peak power produced during the power-load curve. However, only the HIPT group improved significantly MAS (p ≤ 0.05). There were no changes in any variables in CG. Hence, our results suggest that HIPT may be as effective as TPT for improving power performance in young adults. In addition, only HIPT elicited improvements in MAS.


The impact of Alzheimer's disease risk factors on the pupillary light response.
Alzheimer's disease (AD) is the leading cause of dementia, and its prevalence is increasing and is expected to continue to increase over the next few decades. Because of this, there is an urgent requirement to determine a way to diagnose the disease, and to target interventions to delay and ideally stop the onset of symptoms, specifically those impacting cognition and daily livelihood. The pupillary light response (PLR) is controlled by the sympathetic and parasympathetic branches of the autonomic nervous system, and impairments to the pupillary light response (PLR) have been related to AD. However, most of these studies that assess the PLR occur in patients who have already been diagnosed with AD, rather than those who are at a higher risk for the disease but without a diagnosis. Determining whether the PLR is similarly impaired in subjects before an AD diagnosis is made and before cognitive symptoms of the disease begin, is an important step before using the PLR as a diagnostic tool. Specifically, identifying whether the PLR is impaired in specific at-risk groups, considering both genetic and non-genetic risk factors, is imperative. It is possible that the PLR may be impaired in association with some risk factors but not others, potentially indicating different pathways to neurodegeneration that could be distinguished using PLR. In this work, we review the most common genetic and lifestyle-based risk factors for AD and identify established relationships between these risk factors and the PLR. The evidence here shows that many AD risk factors, including traumatic brain injury, ocular and intracranial hypertension, alcohol consumption, depression, and diabetes, are directly related to changes in the PLR. Other risk factors currently lack sufficient literature to make any conclusions relating directly to the PLR but have shown links to impairments in the parasympathetic nervous system; further research should be conducted in these risk factors and their relation to the PLR.


Curved computational integral imaging reconstruction technique for resolution-enhanced display of three-dimensional object images.
A novel curved computational integral imaging reconstruction (C-CIIR) technique for the virtually curved integral imaging (VCII) system is proposed, and its performances are analyzed. In the C-CIIR model, an additional virtual large-aperture lens is included to provide a multidirectional curving effect in the reconstruction process, and its effect is analyzed in detail by using the ABCD matrix. With this method, resolution-enhanced 3D object images can be computationally reconstructed from the picked-up elemental images of the VCII system. To confirm the feasibility of the proposed model, some experiments are carried out. Experiments revealed that the sampling rate in the VCII system could be kept at a maximum value within some range of the distance z, whereas in the conventional integral imaging system it linearly decreased as the distance z increased. It is also shown that resolutions of the object images reconstructed by the C-CIIR method have been significantly improved compared with those of the conventional CIIR method.


Near field behavior of SnO(2) particle-layer deposited on standard optical fiber by electrostatic spray pyrolysis method.
We report the emergent optical near field profiles from standard single mode optical fibers on the cleaved end of which were deposited particle layers of SnO(2). The layers, composed of micron and sub-micron sized particles, were deposited by means of Electrostatic Spray Pyrolysis (ESP) technique. Powerful analytical tools such as Atomic Force Microscopy (AFM) and Scanning Near-field Optical Microscopy (SNOM) were used to obtain simultaneously the SnO(2) layers topography and the related optical near field intensity distribution, when the fiber-substrate is illuminated by a light radiation in NIR range. We show that isolated microstructures, positioned in correspondence of the fiber core, reveal highly unusual capability of locally enhancing the collected optical near field. The observed phenomenon leads to new concepts of fiber optic chemical sensors and in fiber microsystems as well.


Endoscopic and histologic diagnosis of Barrett esophagus.
Endoscopy plays an important role in the identification, diagnosis, and treatment of Barrett esophagus. Short-segment (<2-3 cm) and traditional long-segment (>2-3 cm) Barrett esophagus are distinguished solely on the length of metaplastic tissue above the esophagogastric junction. The histologic hallmark of intestinal metaplasia is required to confirm diagnosis. Biopsy specimens obtained from tissue of presumed Barrett esophagus or an irregular Z line confirm metaplastic glandular mucosa and permit evaluation of dysplastic or neoplastic changes. In the appropriate clinical setting, the use of adjunctive diagnostic techniques may facilitate the diagnosis of Barrett esophagus and sequelae such as dysplasia. Chromoendoscopy with high-resolution or magnified endoscopy is simple, safe, and desirable for surveillance but requires additional procedural time. The use of light-induced fluorescence endoscopy and light-scattering spectroscopy (i.e., optical biopsy) is appealing for the diagnosis and characterization of suspicious lesions. Adjunctive endoscopic techniques and adherence to a protocol for performing biopsies facilitate the early detection and subsequent surveillance of Barrett esophagus.


Comparative behavior of lysosomes and the pre-lysosome compartment (PLC) in in vivo cell fusion experiments.
Interspecies cell fusion was used to compare protein intermixing within the mannose 6-phosphate receptor (MPR)-enriched pre-lysosome compartment (PLC) and within the MPR-negative lysosomal compartment. Both compartments were positive for lysosomal glycoprotein (lgp) membrane markers but were morphologically distinct. In most experiments, rat-mouse cell syncytia were formed by u.v.-inactivated Sindbis virus-mediated fusion. By immunogold electron microscopy of syncytia, extensive intermixing of species-specific lysosomal membrane proteins was observed in both lysosomes and PLC. At 3 h post cell fusion, multiple-label immunogold studies showed that 82% of the lysosome-like structures positive for the rat lysosomal membrane protein LIMP-I were also positive for the mouse lysosomal membrane protein mLAMP-1. By immunofluorescence, LIMP-I and mLAMP-1 co-localized with a t1/2 of 30 min after cell fusion; although the lgp-positive organelle populations had evidently interchanged their proteins, the lysosomal structures remained small, punctate bodies distributed throughout the syncytoplasm as observed in single cells. In contrast, the initially separate units of the PLC congregated with a t1/2 of 1 h to form large, pre-lysosome complexes associated with individual nuclear clusters. At the electron-microscope level, gold markers endocytized by the rat and mouse parent cells in a 1 h uptake followed by a 16-20 h chase co-localized in these extended PLC complexes, as did the membrane markers mLAMP-1 and LIMP-I. The density of labeling for rat MPR in the extended PLCs was markedly decreased, consistent with membrane fusions and dilution of the antigen upon congregation of the PLC compartments from the donor cells. The extended PLC complex behaved as a late endocytic compartment, as shown by co-localization of the MPR and rhodamine-dextran following a 10 min dextran uptake and a 50 min chase. These differences in behavior between lysosomes and the PLC in rat-mouse cell syncytia suggest that the pathway(s) of protein intermixing with respect to the two organelles may be different.


Clinical trials in zirconia: a systematic review.
Zirconia is unique in its polymorphic crystalline makeup, reported to be sensitive to manufacturing and handling processes, and there is debate about which processing method is least harmful to the final product. Currently, zirconia restorations are manufactured by either soft or hard-milling processes, with the manufacturer of each claiming advantages over the other. Chipping of the veneering porcelain is reported as a common problem and has been labelled as its main clinical setback. The objective of this systematic review is to report on the clinical success of zirconia-based restorations fabricated by both milling processes, in regard to framework fractures and veneering porcelain chipping. A comprehensive review of the literature was completed for in vivo trials on zirconia restorations in MEDLINE and PubMed between 1950 and 2009. A manual hand search of relevant dental journals was also completed. Seventeen clinical trials involving zirconia-based restorations were found, 13 were conducted on fixed partial dentures, two on single crowns and two on zirconia implant abutments, of which 11 were based on soft-milled zirconia and six on hard-milled zirconia. Chipping of the veneering porcelain was a common occurrence, and framework fracture was only observed in soft-milled zirconia. Based on the limited number of short-term in vivo studies, zirconia appears to be suitable for the fabrication of single crowns, and fixed partial dentures and implant abutments providing strict protocols during the manufacturing and delivery process are adhered to. Further long-term prospective studies are necessary to establish the best manufacturing process for zirconia-based restorations.


Supramolecular shape memory hydrogels: a new bridge between stimuli-responsive polymers and supramolecular chemistry.
Supramolecular shape memory hydrogels (SSMHs) refer to shape memory polymers, in which temporary shapes are stabilized by reversible crosslinks such as supramolecular interactions and dynamic covalent bonds. Following a brief introduction of the conventional shape memory polymers (SMPs), this tutorial review is focused to summarize the recent advancement in various reversible crosslinks employed to construct SSMHs (supramolecular interactions and dynamic covalent bonds) and different shape memory behaviors (dual and triple shape memory effects). In addition, current challenges and future perspectives in this field are also discussed to suggest a new developing direction.


Chemical Constituents and Their Biological Activities from Genus Styrax.
Plants from the genus Styrax have been extensively used in folk medicines to treat diseases such as skin diseases and peptic ulcers and as an antiseptic and analgesic. Most Styrax species, especially Styrax tonkinensis, which is used as an expectorant, antiseptic, and analgesic in Chinese traditional medicine, could screen resin after external injury. Styrax is also used in folk medicines in Korea to treat sore throat, bronchitis, cough, expectoration, paralysis, laryngitis, and inflammation. Different parts of various Styrax species can be widely employed for ethnopharmacological applications. Moreover, for ethnopharmacological use, these parts of Styrax species can be applied in combination with other folk medicines. Styrax species consist of versatile natural compounds, with some of them exhibiting particularly excellent pharmacological activities, such as cytotoxic, acetylcholinesterase inhibitory, antioxidant, and antifungal activities. Altogether, these exciting results indicate that a comprehensive review of plants belonging to this genus is essential for helping researchers to continuously conduct an in-depth investigation. In this review, the traditional uses, phytochemistry, corresponding pharmacological activities, and structure-activity relationships of different Styrax species are clarified and critically discussed. More insights into potential opportunities for future research are carefully assessed.


Tyrosine 220 in the 5th transmembrane domain of the neuromedin B receptor is critical for the high selectivity of the peptoid antagonist PD168368.
Peptoid antagonists are increasingly being described for G protein-coupled receptors; however, little is known about the molecular basis of their binding. Recently, the peptoid PD168368 was found to be a potent selective neuromedin B receptor (NMBR) antagonist. To investigate the molecular basis for its selectivity for the NMBR over the closely related receptor for gastrin-releasing peptide (GRPR), we used a chimeric receptor approach and a site-directed mutagenesis approach. Mutated receptors were transiently expressed in Balb 3T3. The extracellular domains of the NMBR were not important for the selectivity of PD168368. However, substitution of the 5th upper transmembrane domain (uTM5) of the NMBR by the comparable GRPR domains decreased the affinity 16-fold. When the reverse study was performed by substituting the uTM5 of NMBR into the GRPR, a 9-fold increase in affinity occurred. Each of the 4 amino acids that differed between NMBR and GRPR in the uTM5 region were exchanged, but only the substitution of Phe(220) for Tyr in the NMBR caused a decrease in affinity. When the reverse study was performed to attempt to demonstrate a gain of affinity in the GRPR, the substitution of Tyr(219) for Phe caused an increase in affinity. These results suggest that the hydroxyl group of Tyr(220) in uTM5 of NMBR plays a critical role for high selectivity of PD168368 for NMBR over GRPR. Receptor and ligand modeling suggests that the hydroxyl of the Tyr(220) interacts with nitrophenyl group of PD168368 likely primarily by hydrogen bonding. This result shows the selectivity of the peptoid PD168368, similar to that reported for numerous non-peptide analogues with other G protein-coupled receptors, is primarily dependent on interaction with transmembrane amino acids.


CRISPR-Cas: an adaptive immunity system in prokaryotes.
Most of the archaea and numerous bacteria possess an elaborate system of adaptive immunity to mobile genetic elements known as the CRISPR (clustered regularly interspaced short palindromic repeats)-associated system (CRISPR-Cas), which consists of arrays of short repeats interspersed with unique DNA spacers and adjacent operons encompassing CRISPR-associated (cas) genes with predicted and, in some cases, experimentally validated nuclease, helicase, and polymerase activities. The system functions by integrating fragments of alien DNA between the repeats and employing their transcripts to degrade the DNA of the respective invading elements via an RNA interference-like mechanism. The CRISPR-Cas system is a case of apparent Lamarckian inheritance.


The impact of language on the equivalence of trail making tests: findings from three pediatric cohorts with different language dominance.
The effect of different language backgrounds on performance and the functional equivalence of trail making tests were examined. The children's version of the Trail Making Test A and B (TMT) and the Children's Color Trails Test 1 and 2 (CCTT) were employed with right-handed (n = 79) participants. Children were classified into three groups according to language proficiency: Chinese dominant (CDL), Chinese-English bilinguals (CEB), and English dominant (EDL). In general, the CDL group exhibited the best performance on Children's Color Trails 1 and 2 and Trail Making Test A and B. In examining the functional equivalence of TMT and CCTT, both tests were influenced by language background and intelligence but not gender. The results suggest that language backgrounds do exert a modest effect on trail making tests and that diverging executive demands on CCTT 2 versus TMT B may impact their functional equivalence with different groups of participants. Therefore, caution should be exercised when comparing or replacing CCTT with TMT in children from different and diverging language backgrounds.


First Report of the Introduction of an Exotic Tick, Amblyomma coelebs (Acari: Ixodidae), Feeding on a Human Traveler Returning to the United States from Central America.
Introduction of ticks into the United States that can carry disease-causing pathogens to humans, companion animals, and wildlife has accelerated in recent years, mostly due to globalization, frequency of travel, and a rise in legal and illegal animal trades. We hereby report for the first time introduction of a live fully engorged Amblyomma coelebs feeding on a human into the United States from Central America. Amblyomma coelebs is geographically distributed in the Neotropical region and reaches the southern states of Mexico. This species is capable of transmitting a number of pathogens of public health and veterinary importance including spotted fever group rickettsiae, raising concern that A. coelebs, if it became established in the United States, might also be able to carry these pathogens. Considering the risks of exotic ticks as vectors of numerous pathogens and their potential to establish new populations under conducive climatic and habitat conditions, rigorous inspection practices of imported livestock and pet animals at ports of entry are vital. It is also important for travelers and practitioners to develop a heightened awareness of the public health risks associated with the unintended importation of exotic ticks and the potential such parasites have for breaching United States biosecurity defenses.


Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients.
Leptin, the gene product of the ob gene, is important in the control of appetite in rodents and may have an important role in humans. The clearance of leptin from the circulation is unknown. As the leptin receptor is present in the kidney, we evaluated the role of the kidney in removing circulating leptin in humans. We measured leptin in aortic and renal vein plasma in 8 patients with intact renal function and 6 patients with impaired renal function who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. In patients with intact renal function there is net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal failure on hemodialysis, peripheral leptin levels factored for body mass index was increased by > fourfold as compared to a group of healthy controls (N = 338). In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Additional studies are required to evaluate the role of leptin in mediating the anorexia of uremia.


A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection.
A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States. Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time. Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations. While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice.


Closer Look at the Calorimetric Lower Transition in Lipid Bilayers.
The thermal behavior of unilamellar vesicles has been revisited with differential scanning calorimetry to address the issue of whether it is essential to include interactions between neighboring bilayers in theories and simulations of the ripple phase. The issue focuses on the lower, aka pretransition, and the ripple phase that clearly exists between the lower and main transitions in multilamellar vesicles (MLV). We find anomalous thermal behavior in unilamellar vesicles (ULV) beginning at the same temperature as the lower transition in MLVs, but this feature is considerably broadened and somewhat weaker compared to the lower transition in MLVs. We ascribe this to the difficulty of packing a regular ripple pattern on small spheres. In agreement with a few reports of a ripple phase in direct images of single bilayers, we conclude that interactions between neighboring bilayers are not essential for the ripple phase in lipid bilayers.


Opportunities and challenges for robotic-assisted spine surgery: feasible indications for the MAZOR™ X Stealth Edition.
The clinical use of new technologies has several potential benefits including improved accuracy, precision and efficiency. Robotic assistance during surgery is one such technology and it is making its way into neurosurgical operating rooms with increasing frequency. The Mazor X™ Stealth robot was first used in Canada for spine surgery during July 2022 and since then multiple indications for its use have been identified and evaluated.The outcomes of robot-assisted spine surgery have been promising but there is a lack of supportive studies which would serve to refine indications, establish protocols and disseminate practical information. To begin filling this gap we gathered a list of use-cases for which this new technology was successfully employed. In combination with cases that took place in our Centre, we reviewed the existing reported uses of the Mazor X™ Stealth for spine surgery and recorded their respective procedures and outcomes for patients and surgeons.Through this review we identified common uses of the Mazor X™ Stealth for spine surgery. Usage of robotic-assisted technology had a net positive impact on outcomes for patients as well as surgeons (e.g., improved accuracy of pedicle screw placement and reduced radiation burden). This curation remains a dynamic list, and we foresee the addition of more indications in the future.Clinical Relevance- Enabling the use of technology including robotic systems has the potential to attract clinical research expertise, reduce resource usage and to improve surgical outcomes.


Treatment efficacy of 532-nm diode laser glottoplasty in patients with sulcus vocalis: a prospective study.
This study prospectively assessed the efficacy and safety of 532-nm diode laser glottoplasty in patients with sulcus vocalis. A prospective human trial was performed from August 2016 to September 2021. 532-nm diode laser glottoplasty was performed in 30 consecutive patients with sulcus vocalis who suffered from voice problems. Patients underwent acoustic aerodynamic, perceptual, stroboscopic, and Voice Handicap Index-10 (VHI-10) evaluations before and 1, 6, and 12 months after laser glottoplasty. Most subjective parameters showed significant improvement (P < 0.05) at 6 months after laser glottoplasty and remained stable at 12 months. Most objective parameters showed significant improvement (P < 0.05) at 12 months after laser glottoplasty. Complications during follow-up included mild vocal fold vibration reduction in 3.3% of patients (1/30) and persistent vocal fold edema in 3.3% of patients (1/30). Statistically significant voice improvement at 12 months after 532-nm diode laser glottoplasty was achieved without serious complications.


Genome-wide analysis of chromatin structure changes upon MyoD binding in proliferative myoblasts during the cell cycle.
MyoD, a myogenic differentiation protein, has been studied for its critical role in skeletal muscle differentiation. MyoD-expressing myoblasts have a potency to be differentiated with proliferation of ectopic cells. However, little is known about the effect on chromatin structure of MyoD binding in proliferative myoblasts. In this study, we evaluated the chromatin structure around MyoD-bound genome regions during the cell cycle by chromatin immunoprecipitation sequencing. Genome-wide analysis of histone modifications was performed in proliferative mouse C2C12 myoblasts during three phases (G1, S, G2/M) of the cell cycle. We found that MyoD-bound genome regions had elevated levels of active histone modifications, such as H3K4me1/2/3 and H3K27ac, compared with MyoD-unbound genome regions during the cell cycle. We also demonstrated that the elevated H3K4me2/3 modification level was maintained during the cell cycle, whereas the H3K27ac and H3K4me1 modification levels decreased to the same level as MyoD-unbound genome regions during the later phases. Immunoblot analysis revealed that MyoD abundance was high in the G1 phase then decreased in the S and G2/M phases. Our results suggest that MyoD binding formed selective epigenetic memories with H3K4me2/3 during the cell cycle in addition to myogenic gene induction via active chromatin formation coupled with transcription.


Diabetes, fasting blood glucose and age-related cataract: the Blue Mountains Eye Study.
To examine the relationship between diabetes and the presence of cortical, nuclear and posterior subcapsular (PSC) cataract in a defined older population, while controlling for known cataract risk factors. Slit-lamp and retroillumination lens photographs were taken on 3654 participants attending the population-based Blue Mountains Eye Study during 1992-94. Masked grading of the photographs was performed using the Wisconsin Cataract Grading System. 217 subjects (5.9% of the population) had previously diagnosed diabetes and 66 (1.8%) had diabetes diagnosed from fasting blood glucose measurements. Cortical cataract, PSC and past cataract surgery were associated with known diabetes in age-sex adjusted models. However, only PSC (odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.1) and past cataract surgery (OR 2.5, CI 1.5-4.2) remained statistically significantly associated with diabetes after further adjustment for other known cataract risk factors. Increasing therapy, as an index of diabetes severity (oral or insulin treatment, compared to treatment by diet alone), was associated with a markedly increased risk of PSC (OR 5.4). These findings support previous research showing that diabetes has a harmful effect on the lens. The markedly increased risk for PSC may also have been reflected in the association found between diabetes and past cataract surgery. Contrary to findings from the Beaver Dam Eye Study, we found only a weak association with cortical cataract, which was not statistically significant after adjusting for other known cataract risk factors.


Centrosome motility is essential for initial axon formation in the neocortex.
The mechanisms underlying the normal development of neuronal morphology remain a fundamental question in neurobiology. Studies in cultured neurons have suggested that the position of the centrosome and the Golgi may predict the site of axon outgrowth. During neuronal migration in the developing cortex, however, the centrosome and Golgi are oriented toward the cortical plate at a time when axons grow toward the ventricular zone. In the current work, we use in situ live imaging to demonstrate that the centrosome and the accompanying polarized cytoplasm exhibit apical translocation in newborn cortical neurons preceding initial axon outgrowth. Disruption of centrosomal activity or downregulation of the centriolar satellite protein PCM-1 affects axon formation. We further show that downregulation of the centrosomal protein Cep120 impairs microtubule organization, resulting in increased centrosome motility. Decreased centrosome motility resulting from microtubule stabilization causes an aberrant centrosomal localization, leading to misplaced axonal outgrowth. Our results reveal the dynamic nature of the centrosome in developing cortical neurons, and implicate centrosome translocation and microtubule organization during the multipolar stage as important determinants of axon formation.


Neuroimaging measures of iron and gliosis explain memory performance in aging.
Evidence from animal and histological studies has indicated that accumulation of iron in the brain results in reactive gliosis that contributes to cognitive deficits. The current study extends these findings to human cognitive aging and suggests that magnetic resonance imaging (MRI) techniques like quantitative relaxometry can be used to study iron and its effects in vivo. The effects of iron on microstructure and memory performance were examined using a combination of quantitative relaxometry and multicompartment diffusion imaging in 35 young (21.06 ± 2.18 years) and 28 older (72.58 ± 6.47 years) adults, who also completed a memory task. Replicating past work, results revealed age-related increases in iron content (R2*) and diffusion, and decreases in memory performance. Independent of age group, iron content was significantly related to restricted (intracellular) diffusion in regions with low-moderate iron (hippocampus, caudate) and to all diffusion metrics in regions with moderate-high iron (putamen, globus pallidus). This pattern is consistent with different stages of iron-related gliosis, ranging from astrogliosis that may influence intracellular diffusion to microglial proliferation and increased vascular permeability that may influence all sources of diffusion. Further, hippocampal restricted diffusion was significantly related to memory performance, with a third of this effect related to iron content; consistent with the hypothesis that higher iron-related astrogliosis in the hippocampus is associated with poorer memory performance. These results demonstrate the sensitivity of MRI to iron-related gliosis and extend our understanding of its impact on cognition by showing that this relationship also explains individual differences in memory performance.


Frontal Assessment Battery (FAB) is a simple tool for detecting executive deficits in chronic cannabis users.
Cannabis is the most used illicit drug in the world, and its use has been associated with prefrontal cortex (PFC) dysfunction, including deficits in executive functions (EF). Considering that EF may influence treatment outcome, it would be interesting to have a brief neuropsychological battery to assess EF in chronic cannabis users (CCU). In the present study, the Frontal Assessment Battery (FAB), a brief, easy to use neuropsychological instrument aimed to evaluate EF, was used to evaluate cognitive functioning of CCU. We evaluated 107 abstinent CCU with the FAB and compared with 44 controls matched for age, estimated IQ, and years of education. CCU performed poorly as compared to controls (FAB total score = 16.53 vs. 17.09, p < .05). CCU had also a poor performance in the Motor Programming subtest (2.47 vs. 2.73, p < .05). This study examined effects of cannabis in executive functioning and showed evidence that the FAB is sensitive to detect EF deficits in early abstinent chronic cannabis users. Clinical significance of these findings remains to be investigated in further longitudinal studies. FAB may be useful as a screening instrument to evaluate the necessity for a complete neuropsychological assessment in this population.


Multi-institutional analysis of localized renal cell carcinoma that demonstrates the impact of diabetic status on prognosis after nephrectomy.
The purpose of our study was to determine whether preoperative diabetes mellitus (DM) can predict the prognosis of localized clear-cell renal cell carcinoma (RCC). At five institutes, 2,597 patients with pT1 and pT2 clear-cell RCC were enrolled. Univariate and multivariable analyses were performed to determine factors that associated with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). To identify the effect of DM on survival after recurrence, a subgroup of 127 patients who had recurrences was analyzed. In total, 357 patients had DM. Compared with patients without DM, these patients were older, more likely to be male, and had a higher body mass index, lower GFR, and higher incidence of hypertension. Kaplan-Meier curves showed that patients with DM had a significantly worse rate of RFS, CSS, and OS than patients without DM (log-rank test, all P < 0.05). Multivariate analysis revealed that DM was an independent prognostic factor in terms of RFS, CSS, and OS. In the subgroup analysis of 127 patients with recurrence, DM was associated with a lower survival rate after the initial recurrence. DM appeared to be an important determinant of prognosis in clear-cell localized RCC, especially in patients experiencing recurrence.


Greater distance to an academic medical center is associated with poorer melanoma prognostic factors: The University of Colorado Experience.
Numerous studies report a correlation between distance to diagnostic provider in an academic medical center and poorer prognosis ofdisease. Limited research on this topic exists with respect to melanoma. This was a retrospective chart review of 1,463 adults (≥18 years) initially diagnosed with melanoma between 2006-2016. Associations between distance traveled and Breslow depth and presence of metastatic disease were assessed via cumulative and binary logistic regression models, adjusting for patient and tumor characteristics. Subjects traveling ≥50 miles had 58% greater odds of having an increased Breslow depth than those traveling less than that distance (OR: 1.58; 95% CI: 1.24-2.01; p<0.0001), and had four times the odds of presenting with metastatic disease (OR: 4.04; 95% CI: 3.00-5.46; p<0.0001). We highlight the correlation between increased distance to our academic medical center with greater Breslow depths and the presence ofmetastatic disease at presentation. Future studies assessing other factors and regional differences that limit access to diagnosis might help improve screening efforts to prevent poorer prognosis for patients in these areas.


Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis.
To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant-induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine-xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.


Health promotion interventions for increasing stroke awareness in ethnic minorities: a systematic review of the literature.
Stroke places a significant burden to all affected individuals, but it is perhaps more significant amongst members of black, minority and ethnic communities, who may experience poorer awareness of stroke symptoms than the general population. Recently, several initiatives tried to improve public awareness that symptoms of stroke need to be treated as a medical emergency. However, ethnic communities present cultural barriers, requiring tailored health promotion interventions, whose effectiveness remains uncertain. Our systematic review aimed to identify relevant published evidence, synthesize the main study components and identify evidence of the effectiveness of the interventions. MEDLINE, EMBASE, CINAHL, and PsycInfo were searched for journal articles on health promotion interventions for increasing stroke awareness in ethnic minorities, published in English between 1995 and 2012. Search results were collaboratively assessed by the authors; included studies were analysed to identify their main characteristics, and a thematic analysis of their content was conducted. No meta-analysis was performed, due to the heterogeneity of results. Eighteen studies were included, reporting 15 interventions conducted in the US, for African-Americans or Hispanics; populations sizes differed between interventions. Interventions were mostly carried out in community settings with different educational techniques, focussing on experiential methods. Health professionals usually organized the programs, delivered by nurses, other health professionals or volunteers.The few theory-based interventions focussed on individual-level behavioural change. Practical cultural adaptation strategies were not linked to specific theoretical frameworks. Interventions widely differed as for target populations, settings, delivery methods, contents and professional roles involved. All study designs were quantitative, and the emerging evidence of effectiveness was inconclusive.Such interventions operate in very complex scenarios, and several variables may influence their effectiveness. Therefore, qualitative or mixed-methods study designs may shed light on barriers and facilitators, experiential education strategies and community involvement.Network- and community-level theories may help improving design and evaluation of interventions. Eleven case reports and four RCTs provide evidence about stroke awareness interventions organized in the US. The studies provide only partial and inconclusive evidence about the effectiveness of the interventions. Hence, further research is needed on different countries and ethnic minorities.


Growing challenges for HIV programmes in Asia: clinic population trends, 2003-2013.
The scale-up of antiretroviral therapy (ART) has led to a substantial change in the clinical population of HIV-positive patients receiving care. We describe the temporal trends in the demographic and clinical characteristics of HIV-positive patients initiating ART in 2003-13 within an Asian regional cohort. All HIV-positive adult patients that initiated ART between 2003 and 2013 were included. We summarized ART regimen use, age, CD4 cell count, HIV viral load, and HIV-related laboratory monitoring rates during follow-up by calendar year. A total of 16 962 patients were included in the analysis. Patients in active follow-up increased from 695 patients at four sites in 2003 to 11,137 patients at eight sites in 2013. The proportion of patients receiving their second or third ART regimen increased over time (5% in 2003 to 29% in 2013) along with patients aged ≥50 years (8% in 2003 to 18% in 2013). Concurrently, CD4 monitoring has remained stable in recent years, whereas HIV viral load monitoring, although varied among the sites, is increasing. There have been substantial changes in the clinical and demographic characteristics of HIV-positive patients receiving ART in Asia. HIV programmes will need to anticipate the clinical care needs for their aging populations, expanded viral load monitoring, and, the eventual increase in second and third ART regimens that will lead to higher costs and more complex drug procurement needs.


Bacterial extracellular vesicles affect endocrine therapy in MCF7 cells.
: The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.


Screening, gene cloning, and characterization of orsellinic acid decarboxylase from Arthrobacter sp. K8 for regio-selective carboxylation of resorcinol derivatives.
Toward a sustainable synthesis of value-added chemicals, the method of CO2 utilization attracts great interest in chemical process engineering. Biotechnological CO2 fixation is a promising technology; however, efficient methods that can fix carbon dioxide are still limited. Instead, some parts of microbial decarboxylases allow the introduction of carboxy group into phenolic compounds using bicarbonate ion as a C1 building block. Here, we identified a unique decarboxylase from Arthrobacter sp. K8 that acts on resorcinol derivatives. A high-throughput colorimetric decarboxylase assay facilitated gene cloning of orsellinic acid decarboxylase from genomic DNA library of strain K8. Sequence analysis revealed that the orsellinic acid decarboxylase belonged to amidohydrolase 2 family, but shared low amino acid sequence identity with those of related decarboxylases. Enzymatic characterization unveiled that the decarboxylase introduces a carboxy group in a highly regio-selective manner. We applied the decarboxylase to enzymatic carboxylation of resorcinol derivatives. Using Escherichia coli expressing the decarboxylase gene as a whole cell biocatalyst, orsellinic acid, 2,4-dihydroxybenzoic acid, and 4-methoxysalicylic acid were produced in the presence of saturated bicarbonate. These findings could provide new insights into the production of useful phenolic acids from resorcinol derivatives.


Allergic reaction to nickel orthodontic wires: a case report.
A 14-year-old boy had an allergic reaction to nickel wires used in an orthodontic appliance. The allergy was confirmed through patch testing.


Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma.
: TRIM29 (tripartite motif-containing protein 29) is a TRIM family protein that has been implicated in breast, colorectal, and pancreatic cancers. However, its role in stratified squamous epithelial cells and tumors has not been elucidated. Here, we investigate the expression of TRIM29 in cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers. TRIM29 expression was lower in malignant SCC lesions than in adjacent normal epithelial tissue or benign tumors. Lower expression of TRIM29 was associated with higher SCC invasiveness. Primary tumors of cutaneous SCC showed aberrant hypermethylation of TRIM29. Depletion of TRIM29 increased cancer cell migration and invasion; conversely, overexpression of TRIM29 suppressed these. Comprehensive proteomics and immunoprecipitation analyses identified keratins and keratin-interacting protein FAM83H as TRIM29 interactors. Knockdown of TRIM29 led to ectopic keratin localization of keratinocytes. In primary tumors, lower TRIM29 expression correlated with the altered expression of keratins. Our findings reveal an unexpected role for TRIM29 in regulating the distribution of keratins, as well as in the migration and invasion of SCC. They also suggest that the TRIM29-keratin axis could serve as a diagnostic and prognostic marker in stratified epithelial tumors and may provide a target for SCC therapeutics. SIGNIFICANCE: These findings identify TRIM29 as a novel diagnostic and prognostic marker in stratified epithelial tissues.


Impact of the COVID-19 pandemic on vaccine coverage for early childhood vaccines in Alberta, Canada: a population-based retrospective cohort study.
To assess the impact of the COVID-19 pandemic on early childhood vaccination coverage in Alberta, Canada. Alberta, a western Canadian province, which has a population of 4.4 million and approximately 50 000 births annually. In this retrospective cohort study, population-based administrative health data were analysed to determine the vaccination coverage for measles-containing, pertussis-containing and rotavirus vaccines. We measured monthly and cumulative vaccine coverage. We assessed the absolute difference in monthly and cumulative coverage for each vaccine dose by comparing children due for vaccination in each month of 2019 and 2020, with follow-up to determine if missed doses were caught up later. We included 114 178 children in the 2019 analysis cohort and 106 530 children in the 2020 analysis cohort. Monthly vaccination coverage in 2020 was higher than 2019 until March, when coverage significantly declined. Comparing April 2020 to 2019, coverage was 9.9% (95% CI 7.9% to 12.0%) lower for measles vaccine; 4.9% (95% CI 3.3% to 6.5%), 7.1% (95% CI 5.2% to 9.1%), 5.2% (95% CI 3.1% to 7.4%) and 8.8% (95% CI 6.6% to 10.9%) lower for first, second, third and fourth doses of pertussis-containing vaccine, respectively; and 4.0% (95% CI 2.3% to 5.7%), 7.1% (95% CI 5.1% to 9.2%) and 4.6% (95% CI 2.4% to 6.7%) lower for first, second and third doses of rotavirus vaccine, respectively. Monthly coverage improved during May to July 2020; however, some doses experienced a second decline during September to October 2020. The cumulative coverage analysis showed that the measles-containing vaccine had the largest difference in coverage at the end of follow-up. Children who were due for vaccination early in the pandemic and in Fall 2020, especially those due for measles vaccination, may require additional catch-up.


Screening Brazilian commercial gasoline quality by hydrogen nuclear magnetic resonance spectroscopic fingerprintings and pattern-recognition multivariate chemometric analysis.
The identification of gasoline adulteration by organic solvents is not an easy task, because compounds that constitute the solvents are already in gasoline composition. In this work, the combination of Hydrogen Nuclear Magnetic Resonance ((1)H NMR) spectroscopic fingerprintings with pattern-recognition multivariate Soft Independent Modeling of Class Analogy (SIMCA) chemometric analysis provides an original and alternative approach to screening Brazilian commercial gasoline quality in a Monitoring Program for Quality Control of Automotive Fuels. SIMCA was performed on spectroscopic fingerprints to classify the quality of representative commercial gasoline samples selected by Hierarchical Cluster Analysis (HCA) and collected over a 6-month period from different gas stations in the São Paulo state, Brazil. Following optimized the (1)H NMR-SIMCA algorithm, it was possible to correctly classify 92.0% of commercial gasoline samples, which is considered acceptable. The chemometric method is recommended for routine applications in Quality-Control Monitoring Programs, since its measurements are fast and can be easily automated. Also, police laboratories could employ this method for rapid screening analysis to discourage adulteration practices.


Oestrogen, progesterone and stem cells: the discordant trio in endometriosis?
Oestrogen-progesterone signalling is highly versatile and critical for the maintenance of healthy endometrium in humans. The genomic and nongenomic signalling cascades initiated by these hormones in differentiated cells of endometrium have been the primary focus of research since 1920s. However, last decade of research has shown a significant role of stem cells in the maintenance of a healthy endometrium and the modulatory effects of hormones on these cells. Endometriosis, the growth of endometrium outside the uterus, is very common in infertile patients and the elusiveness in understanding of disease pathology causes hindrance in selection of treatment approaches to enhance fertility. In endometriosis, the stem cells are dysfunctional as it can confer progesterone resistance to their progenies resulting in disharmony of hormonal orchestration of endometrial homeostasis. The bidirectional communication between stem cell signalling pathways and oestrogen-progesterone signalling is found to be disrupted in endometriosis though it is not clear which precedes the other. In this paper, we review the intricate connection between hormones, stem cells and the cross-talks in their signalling cascades in normal endometrium and discuss how this is deregulated in endometriosis. Re-examination of the oestrogen-progesterone dependency of endometrium with a focus on stem cells is imperative to delineate infertility associated with endometriosis and thereby aid in designing better treatment modalities.


Technology-Based Mental Health Interventions for Domestic Violence Victims Amid COVID-19.
Domestic violence is a threat to human dignity and public health. Mounting evidence shows that domestic violence erodes personal and public health, spawning issues such as lifelong mental health challenges. To further compound the situation, COVID-19 and societies' poor response to the pandemic have not only worsened the domestic violence crisis but also disrupted mental health services for domestic violence victims. While technology-based health solutions can overcome physical constraints posed by the pandemic and offer timely support to address domestic violence victims' mental health issues, there is a dearth of research in the literature. To bridge the research gap, in this study, we aim to examine technology-based mental health solutions for domestic violence victims amid COVID-19. A literature review was conducted to examine solutions that domestic violence victims can utilize to safeguard and improve their mental health amid COVID-19. Databases including PubMed, PsycINFO, and Scopus were utilized for the literature search. The search was focused on four themes: domestic violence, mental health, technology-based interventions, and COVID-19. A reverse search of pertinent references was conducted in Google Scholar. The social ecological model was utilized to systematically structure the review findings. The findings show that a wide array of technology-based solutions has been proposed to address mental health challenges faced by domestic violence victims amid COVID-19. However, none of these proposals is based on empirical evidence amid COVID-19. In terms of social and ecological levels of influence, most of the interventions were developed on the individual level, as opposed to the community level or social level, effectively placing the healthcare responsibility on the victims rather than government and health officials. Furthermore, most of the articles failed to address risks associated with utilizing technology-based interventions (e.g., privacy issues) or navigating the online environment (e.g., cyberstalking). Overall, our findings highlight the need for greater research endeavors on the research topic. Although technology-based interventions have great potential in resolving domestic violence victims' mental health issues, risks associated with these health solutions should be comprehensively acknowledged and addressed.


Restoration of the crystallization of altered delta-endotoxins Cry1Ac, by the promotion of their in vivo integration into the Bacillus thuringiensis native crystals.
Cry1Ac is one of the most-studied Bacillus thuringiensisdelta-endotoxins. Structurally, it is divided into two domains: the N-terminal half corresponding to the toxic component and the C-terminal half corresponding to the region responsible for the crystal formation. We engineered Cry1Ac delta-endotoxins modified in their N-terminal part and studied the effect of such modifications on crystallization and delta-endotoxin production. When expressed in an acrystalliferous B. thuringiensis strain, Cry1Ac(*) and Cry1AcDelta, variants with four point mutations and a deletion, respectively, could not form crystals. However, when expressed in a crystalliferous strain, these altered proteins were shown to interact with the endogenous delta-endotoxins and cocrystallize with them, forming atypical crystals observed by electron microscopy. This cocrystallization of the altered delta-endotoxins with the endogenous ones led to a decrease in delta-endotoxin production (27%) by the corresponding recombinant B. thuringiensis strains. This ability of altered delta-endotoxins containing an intact C-terminal part to cocrystallize with native ones could be exploited to promote the crystallization of foreign proteins by fusing them with the C-terminal part of Cry1A delta-endotoxins.


Liquid chromatographic determination of benzo[a]pyrene in total particulate matter of cigarette smoke.
The benzo[a]pyrene (BaP) delivery of reference and commercially available tobacco cigarettes, as well as reference and placebo marijuana cigarettes, is determined using a sequential liquid chromatographic/liquid chromatographic procedure. The total particulate matter of sample cigarette smoke is collected using a Cambridge filter pad, which is ultrasonically extracted with acetone. The resulting extract is filtered, then fractionated using semipreparative-scale normal phase liquid chromatography (LC). Quantitative determination is achieved using analytical-scale reverse phase LC equipped with a fluorescence detector. The method is precise (+/- 10-15% relative standard deviation) and yields 85% or better BaP recovery at the ng/cig. level. A single pad may be analyzed in 8 person-hours, while a more typical lot of 12 pads (6 pads each for 2 cigarette brands) may be analyzed in 10 person-days.


The Evolution of Energetic Scaling across the Vertebrate Tree of Life.
Metabolism is the link between ecology and physiology-it dictates the flow of energy through individuals and across trophic levels. Much of the predictive power of metabolic theories of ecology derives from the scaling relationship between organismal size and metabolic rate. There is growing evidence that this scaling relationship is not universal, but we have little knowledge of how it has evolved over macroevolutionary time. Here we develop a novel phylogenetic comparative method to investigate how often and in which clades the macroevolutionary dynamics of the metabolic scaling have changed. We find strong evidence that the metabolic scaling relationship has shifted multiple times across the vertebrate phylogeny. However, shifts are rare and otherwise strongly constrained. Importantly, both the estimated slope and intercept values vary widely across regimes, with slopes that spanned across theoretically predicted values such as 2/3 or 3/4. We further tested whether traits such as ecto-/endothermy, genome size, and quadratic curvature with body mass (i.e., energetic constraints at extreme body sizes) could explain the observed pattern of shifts. Though these factors help explain some of the variation in scaling parameters, much of the remaining variation remains elusive. Our results lay the groundwork for further exploration of the evolutionary and ecological drivers of major transitions in metabolic strategy and for harnessing this information to improve macroecological predictions.


The organization of taste sensibilities in hamster chorda tympani nerve fibers.
Electrophysiological measurements of nerve impulse frequencies were used to explore the organization of taste sensibilities in single fibers of the hamster chorda tympani nerve. Moderately intense taste solutions that are either very similar or easily discriminated were applied to the anterior lingual surface. 40 response profiles or 13 stimulus activation patterns were considered variables and examined with multivariate statistical techniques. Three kinds of response profiles were seen in fibers that varied in their overall sensitivity to taste solutions. One profile (S) showed selectivity for sweeteners, a second (N) showed selectivity for sodium salts, and a third (H) showed sensitivity to salts, acids, and other compounds. Hierarchical cluster analysis indicated that profiles fell into discrete classes. Responses to many pairs of effective stimuli were covariant across profiles within a class, but some acidic stimuli had more idiosyncratic effects. Factor analysis of profiles identified two common factors, accounting for 77% of the variance. A unipolar factor was identified with the N profile, and a bipolar factor was identified with the S profile and its opposite, the H profile. Three stimulus activation patterns were elicited by taste solutions that varied in intensity of effect. Hierarchical cluster analysis indicated that the patterns fell into discrete classes. Factor analysis of patterns identified three common unipolar factors accounting for 82% of the variance. Eight stimuli (MgSO4, NH4Cl, KCl, citric acid, acetic acid, urea, quinine HCl, HCl) selectively activated fibers with H profiles, three stimuli (fructose, Na saccharin, sucrose) selectively activated fibers with S profiles, and two stimuli (NaNO3, NaCl) activated fibers with N profiles more strongly than fibers with H profiles. Stimuli that evoke different patterns taste distinct to hamsters. Stimuli that evoke the same pattern taste more similar. It was concluded that the hundreds of peripheral taste neurons that innervate the anterior tongue play one of three functional roles, providing information about one of three features that are shared by different chemical solutions.


Enhancing physical and psychological functioning in older family caregivers: the role of regular physical activity.
Although informal caregiving among older adults creates a range of physical and psychological burdens for the caregiver, little research has been directed at evaluating strategies for preserving caregivers physical functioning in addition to their psychological well-being. The purpose of the current research was to examine, through population-based survey sampling procedures, levels of physical activity and related health practices and preferences among a random sample of older family caregivers; evaluate, using an experimental design, the feasibility of initiating a four-month supervised home-based moderate-intensity physical activity regimen among older family caregivers; and explore the potential effects of physical activity on anger expression, caregiver burden, and related psychological outcomes in this population. The results suggest that: (a) physical inactivity is a prevalent risk factor among family caregivers that requires systematic attention; (b) a significant proportion of family caregivers of both sexes are interested in improving their physical activity levels, especially through programs that do not require ongoing attendance at a class or group; and (c) supervised home-based programs that focus on brisk walking and similar moderate-intensity physical activities appear to be both feasible and potentially beneficial in health (e.g. ambulatory blood pressure) as well as mental health (e.g. anger expression) areas.


Activation of GPER1 in macrophages ameliorates UUO-induced renal fibrosis.
Numerous studies have proven the critical role of macrophages in the renal fibrosis process. Notably, G Protein-coupled Estrogen Receptor 1 (GPER1), a novel estrogen receptor, has been shown to play a ubiquitous role in regulating macrophage activities and proinflammatory pathways. However, the precise role of GPER1 in macrophage-mediated renal fibrosis is unknown. In this study, we aimed to investigate the function of macrophage GPER1 in the UUO-induced renal fibrosis model. Compared to vehicle-treated ovariectomized (OVX) female and male unilateral ureteral obstruction (UUO) models, we observed that G-1 (GPER1 agonist)-treated OVX female and male UUO mice had fewer renal fibrotic lesions and less M1 and M2 macrophage infiltration in the kidney tissues. Conversely, Gper1 deletion in male UUO mice accelerated renal fibrosis and increased inflammation. In vitro studies also revealed that GPER1 activation reduced M0 macrophage polarization towards M1 or M2 phenotypes. The RNA-sequencing analysis and immunoblotting indicated that GPER1 activation was primarily involved in downregulating immune pathways activation and inactivating MAPK pathways. Tubular epithelial cells co-cultured with G-1-pretreated M1 macrophages exhibited fewer injuries and immune activation. In addition, fibroblasts co-cultured with G-1-pretreated M2 macrophages showed downregulated extracellular matrix expression. Overall, this is the first study to demonstrate the effect of GPER1 on macrophage-mediated renal fibrosis via inhibition of M1 and M2 macrophage activation. These findings indicate that GPER1 may be a promising therapeutic target for treating renal fibrosis.


Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status.
Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due to their rarity, the characterization of the musculo-skeletal phenotype in both disorders has been poorly characterized. Herein we reported data on orthopedic findings and functional status of a large sample of CS and CFCS patients. Thirty-four patients (CS = 17 and CFCS = 17) were recruited. Functional and disability evaluations were performed by assessing the 6-min walking test (6MWT) and Pediatric Outcomes Data Collection Instrument (PODCI). Genotype/phenotype correlation was also provided. Orthopedic manifestations are highly prevalent in CS and CFCS and overlap in the two disorders. Overall, patients with CS harboring the recurrent HRAS Gly12Ser substitution show a more severe skeletal phenotype compared to patients carrying the Gly12Ala and Gly13Cys variants. Among CFCS patients, those with the MAP2K1/2 variant show different skeletal characteristics compared to BRAF variants, with a higher prevalence of orthopedic abnormalities. Functional assessment showed that patients with CS and CFCS reached lower values compared to the general population, with CFCS patients displaying the lowest scores. Orthopedic manifestations appear universal features of CS and CFCS and they can evolve across patients' life. Longitudinal assessment of disability status by using 6MWT and PODCI could be useful to evaluate the functional impact of orthopedic manifestations on patients' outcome and help planning a tailored treatment of these comorbidities.


Modes of cell wall growth differentiation in rod-shaped bacteria.
A bacterial cell takes on the challenge to preserve and reproduce its shape at every generation against a substantial internal pressure by surrounding itself with a mechanical support, a peptidoglycan cell wall. The enlargement of the cell wall via net incorporation of precursors into the pre-existing wall conditions bacterial growth and morphology. However, generation, reproduction and/or modification of a specific shape requires that the incorporation takes place at precise locations for a defined time period. Much has been learnt in the past few years about the biochemistry of the peptidoglycan synthesis process, but topological approaches to the understanding of shape generation have been hindered by a lack of appropriate techniques. Recent technological advances are paving the way for substantial progress in understanding the mechanisms of bacterial morphogenesis. Here we review the latest developments, focusing on the impact of new techniques on the precise mapping of cell wall growth sites.


Phosphorylation of PUF-A/PUM3 on Y259 modulates PUF-A stability and cell proliferation.
Human PUF-A/PUM3 is a RNA and DNA binding protein participating in the nucleolar processing of 7S to 5.8S rRNA. The nucleolar localization of PUF-A redistributes to the nucleoplasm upon the exposure to genotoxic agents in cells. However, little is known regarding the roles of PUF-A in tumor progression. Phosphoprotein database analysis revealed that Y259 phosphorylation of PUF-A is the most prevalent residue modified. Here, we reported the importance of PUF-A's phosphorylation on Y259 in tumorigenesis. PUF-A gene was knocked out by the Crispr/Cas9 method in human cervix epithelial HeLa cells. Loss of PUF-A in HeLa cells resulted in reduced clonogenic and lower transwell invasion capacity. Introduction of PUF-AY259F to PUF-A deficient HeLa cells was unable to restore colony formation. In addition, the unphosphorylated mutant of PUF-A, PUF-AY259F, attenuated PUF-A protein stability. Our results suggest the important role of Y259 phosphorylation of PUF-A in cell proliferation.